The cardinal property of pancreatic beta cells, shared by no other cell in the body, is high level expression of the insulin gene. The cis and trans elements that affect insulin promoter activity have been studied for many years but it is clear that our understanding is limited. In particular, while the promoter elements that determine beta-cell specificity of insulin expression are well understood, the pathways that signal to the insulin promoter have not been investigated extensively, in part because of a lack of in vitro models. There is a need for effective screening methods in order to identify substances, e.g., chemical compounds, that modulate insulin production, that is, increase or decrease insulin production.